Configuring a deep brain stimulation (dbs) system to treat a neurological disorder

ABSTRACT

Deep brain stimulation (DBS) can be used to treat many neurological conditions beyond traditional movement disorders. When patients do not suffer from traditional movement disorders, medical professionals cannot use traditional observation-based methods to configure the DBS system. A new method for selecting stimulation configurations can include recording internal data and external data as the patient performs (or attempts to perform) a motor task. The internal data is electrophysiology data recorded by a plurality of DBS electrodes, used to identify at least one of the plurality of electrodes closest to a neuronal population involved in control of the at least one motor task. The external data is electroencephalogram (EEG) data recorded by scalp electrodes, which is used to select at least one of the potential stimulation electrodes to deliver the DBS. When the electrode(s) delivering the DBS are selected, optimal parameters for the DBS are then chosen.

RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application Ser.No. 62/964,710, filed Jan. 23, 2020, entitled “Biomarkers for DBSProgramming and Control”. The entirety of this provisional applicationis hereby incorporated by reference for all purposes.

GOVERNMENT SUPPORT

This invention was made with government support under NS100543 awardedby the National Institutes of Health. The government has certain rightsin this invention.

TECHNICAL FIELD

The present disclosure relates generally to deep brain stimulation (DBS)and, more specifically, to systems and methods for configuring a DBSsystem to stimulate a cerebellar pathway connecting to a brainstem, adiencephalon, or a cerebrum of a patient to treat a neurologicaldisorder in the patient.

BACKGROUND

For years, deep brain stimulation (DBS) has been used to controlspurious brain activity causing unwanted movements connected to movementdisorders, such as Parkinson's disease and essential tremor. DBSelectrodes have been implanted in a patient's brain in one or more areasknown to experience the spurious brain activity and one or more of theseDBS electrodes can be used to deliver electrical stimulation to the oneor more areas. The electrical stimulation can be specifically configuredto modulate the spurious brain activity, thereby reducing the unwantedmovements (e.g., tremor, rigidity, and the like).

A medical professional can observe when the unwanted movement stops, soconfiguration of the DBS system and the electrical stimulation isstraightforward. The medical professional tests a series of settings andobserves the corresponding improvement or worsening of symptoms of theunwanted movement. These settings can be programmed into the DBS system,leading to good management of the unwanted movement over a long term.When DBS is used for purposes other than stopping unwanted movement,however, the stimulation settings cannot be chosen based on observationalone. When DBS is used to stimulate a cerebellar pathway connecting toa brainstem, a diencephalon, or a cerebrum to treat differentneurological conditions, different methods must be used to find thestimulation configurations.

SUMMARY

The present disclosure relates to systems and methods for configuring adeep brain stimulation (DBS) system to stimulate a cerebellar pathwayconnecting to a brainstem, a diencephalon, or a cerebrum of a patient totreat a neurological disorder in the patient.

In an aspect, the present disclosure can include a system thatconfigures the DBS system. The system can include a memory storinginstructions and a processor to access the memory and execute theinstructions to: receive electrophysiology data from a plurality ofimplanted DBS electrodes (e.g., implanted in at least one cerebellarpathway connecting to a brainstem, a diencephalon, or a cerebrum of thepatient) and electroencephalogram (EEG) data corresponding to at leastone scalp EEG from a plurality of scalp electrodes in response to thepatient performing or attempting to perform at least one motor task;based on the electrophysiology data, identify at least one of theplurality of electrodes implanted closest to a neuronal populationsinvolved in control of the at least one motor task as potentialstimulation electrodes and based on the EEG data and/orelectrophysiological data from the DBS electrodes, select at least oneof the potential stimulation electrodes to deliver the DBS based onwhich of the potential stimulation electrodes provides a change in theEEG data and/or in the data from the DBS electrodes; and determiningoptimal parameters for the DBS. The optimal parameters for the DBS andthe at least one of the potential stimulation electrode to deliver theDBS are output for guiding configuration of the DBS system for thepatient.

In another aspect, the present disclosure can include a method forconfiguring the DBS system. The method can include instructing thepatient to perform or attempt to perform at least one motor task. Inresponse to the patient performing or attempting to perform the at leastone motor task, a system that includes a processor can execute steps ofthe method, including: receiving electrophysiology data from a pluralityof DBS electrodes implanted in at least one cerebellar pathwayconnecting to a brainstem, a diencephalon, or a cerebrum of the patient;based on the electrophysiology data, identifying, by the system, atleast one of the plurality of electrodes implanted closest to a neuronalpopulations involved in control of the at least one motor task aspotential stimulation electrodes; in response to the patient performingor attempting to perform the at least one motor task, receiving EEG datacorresponding to at least one scalp EEG from a plurality of scalpelectrodes and/or data from at least one DBS electrode; based on the EEGdata and/or DBS electrode data, selecting at least one of the potentialstimulation electrodes to deliver the DBS based on which of thepotential stimulation electrodes provides a change in the EEG dataand/or DBS electrode data; and determining optimal parameters for theDBS by the at least one of the potential stimulation electrodes. Theoptimal parameters for the DBS and the at least one of the potentialstimulation electrode to deliver the DBS are output for guidingconfiguration of the DBS system for the patient.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features of the present disclosure will becomeapparent to those skilled in the art to which the present disclosurerelates upon reading the following description with reference to theaccompanying drawings, in which:

FIG. 1 is a diagram showing an example of a system that can be used toconfigure a DBS system to stimulate a cerebellar pathway connecting to abrainstem, a diencephalon, or a cerebrum of a patient to treat aneurological disorder in the patient in accordance with an aspect of thepresent disclosure;

FIG. 2 shows example inputs and outputs to the controller of FIG. 1;

FIG. 3 shows an example of how the controller can use tuning toconfigure the DBS system;

FIG. 4 is a process flow diagram illustrating a method for configuring aDBS system to stimulate a cerebellar pathway connecting to a brainstem,a diencephalon, or a cerebrum of a patient to treat a neurologicaldisorder in the patient in accordance with another aspect of the presentdisclosure;

FIG. 5 is a process flow diagram illustrating a method showing theapproach for configuring the DBS system used experimentally;

FIG. 6 shows modulation of local field potentials (LFPs) recorded fromthe cerebellar dentate nucleus during performance of a motor task usingan affected extremity;

FIGS. 7 and 8 show modulation of LFPs for different electrodes indifferent patients;

FIG. 9 shows task-related changes and DBS treatment related changes inalpha and beta band activity recorded using scalp electroencephalogram(EEG) electrodes placed over the contralateral sensorimotor cortex;

FIG. 10 shows different changes that occur in motor behavior or metrics;and

FIG. 11 shows the effects of titration to choose some of the parametersof the DBS system.

DETAILED DESCRIPTION I. Definitions

Unless otherwise defined, all technical terms used herein have the samemeaning as commonly understood by one of ordinary skill in the art towhich the present disclosure pertains.

As used herein, the singular forms “a,” “an” and “the” can also includethe plural forms, unless the context clearly indicates otherwise.

As used herein, the terms “comprises” and/or “comprising,” can specifythe presence of stated features, steps, operations, elements, and/orcomponents, but do not preclude the presence or addition of one or moreother features, steps, operations, elements, components, and/or groups.

As used herein, the term “and/or” can include any and all combinationsof one or more of the associated listed items.

As used herein, the terms “first,” “second,” etc. should not limit theelements being described by these terms. These terms are only used todistinguish one element from another. Thus, a “first” element discussedbelow could also be termed a “second” element without departing from theteachings of the present disclosure. The sequence of operations (oracts/steps) is not limited to the order presented in the claims orfigures unless specifically indicated otherwise.

As used herein, the term “deep brain stimulation”, represented by theabbreviation DBS, refers to electrical stimulation applied to targetsites within specific regions of the brain by electrodes implantedwithin the specific regions. In some instances, the electricalstimulation can be chronically applied.

As used herein, the terms “neurological disorder” and “neurologicalcondition” refer to a structural, biochemical, and/or electricalabnormality in the brain, spinal cord, or peripheral nerves. Theneurological condition treated with DBS can be an electrical abnormalitywithin the brain. For example, DBS can be used to stimulate a cerebellarpathway connecting to a brainstem, a diencephalon, or a cerebrum totreat a range of different neurological conditions (e.g., stroke,epilepsy, movement disorders, psychiatric disorders, mood disorders,neurological deficits resulting from trauma/surgical treatment,demyelination, or neurodegeneration, or the like).

As used herein, the term “configure” when used with deep brainstimulation refers to choosing the electrode(s) to deliver the DBS andthe parameters at which the DBS is to be delivered.

As used herein, the term “electrophysiology” refers to measurement ofelectrical activity associated with the nervous system. Theelectrophysiology measurement can be local to one or more parts of thenervous system.

As used herein, the term “local field potential”, represented by theabbreviation LFP, refers to the electric potential recorded in theextracellular space in brain tissue. LFPs are an example ofelectrophysiology data.

As used herein, the term “electroencephalogram”, represented by theabbreviation EEG, refers to signals from the brain recorded by externalelectrodes attached to the scalp (also referred to as EEG scalpelectrodes).

As used herein, the term “motor task” refers to a movement or action ofone or more muscles.

As used herein, the term “titration” refers to a process of configuringa stimulation to reduce symptoms to the greatest possible degree whileavoiding as many side effects as possible.

As used herein, the term “optimal” refers to something that is the mostfavorable. For example, an optimal solution satisfies most or allconditions with no or a small number of negative results.

As used herein, the terms “user” and “patient” can be usedinterchangeably and refer to any warm-blooded organism that may besuffering from a neurological disorder that is treated with DBS.

As used herein, the term “medical professional” refers to any trainedcaregiver, such as a doctor, a medical student, a physician's assistant,a nurse, a technician, or the like.

II. Overview

Traditionally, deep brain stimulation (DBS) has been used on patientswith movement disorders caused by neurological conditions likeParkinson's disease and essential tremor to minimize instances of themovement disorders. In these traditional uses of DBS, a medicalprofessional can visually observe when the unwanted movement reduces,Thus, configuration of the DBS system involves the medical professionaltesting a series of settings and observing the corresponding improvementor worsening of symptoms of the unwanted movement. As the uses of DBSexpand to treat different neurological disorders (e.g., stroke and itssequelae, weakness, epilepsy, cognitive disorders, movement disorders,psychiatric disorders, mood disorders, neurological deficits arisingfrom trauma/surgical treatment, demyelination, neurodegeneration, or thelike) by stimulating a cerebellar pathway connecting to a brainstem, adiencephalon, or a cerebrum, such conventional methods for selecting astimulation configurations become unusable. As an example, the sequelaefrom stroke is one of many indications that can be treated with DBS ofthe cerebellothalamocortical (CTC) pathway, but configuring the DBSsystem for stroke patients by traditional means has proven difficult.

To overcome these challenges associated with configuring DBS tostimulate a cerebellar pathway connecting to a brainstem, adiencephalon, or a cerebrum to treat the neurological disorder in thepatient, the present disclosure relates to systems and methods forconfiguring the DBS system based on biomarkers used to determine optimalstimulation patterns of the DBS on related neural networks (e.g., thecerebellothalamocortical pathways for stroke). The biomarkers arederived from one or more of the following electrophysiological and/orbiomechanical techniques, including electrical stimulation of anycomponent of a neural pathway associated with the neurologicalcondition, internal recordings of electrophysiology of sub-corticalareas and/or deep brain tissue, external recordings of conduction fromthe primary motor cortex, secondary motor cortex, primary sensorycortex, and/or secondary sensory cortex, and mechanical measures whenperforming or attempting to perform at least one motor task with a taskcomponent that can provide a mechanical or digitized measurement ofmovement, including displacement/velocity/acceleration of an extremityor body part, dexterity of an extremity or body part, strength of anextremity or body part, resistance, including rigidity or spasticity, ofan extremity or body part, and electromyography. Described herein is theuse of several of these biomarkers to configure a DBS system tostimulate a cerebellar pathway connecting to a brainstem, adiencephalon, or a cerebrum of a patient to treat a certain neurologicaldisorder in a patient. Specifically internal recordings ofelectrophysiology data, external recordings of EEG data, and mechanicalmeasures. It should be noted that the other biomarkers can be used asnecessary to accomplish this configuration of the DBS system for thepatient.

III. Systems

An aspect of the present disclosure can include a system 10 (FIG. 1)that can be used to configure a DBS system to stimulate a cerebellarpathway connecting to a brainstem, a diencephalon, or a cerebrum of apatient to treat a neurological disorder in the patient. The system caninclude a controller 12 that receives (1) internal 13 data from aneurostimulator 14 (which can be internal to the body and/or external tothe body) regarding data recorded by one or more implanted DBSelectrodes 15 and (2) external 16 data from one or more EEG scalpelectrodes 16 in response to a patient performing a motor task with atask component 18. The controller 12 can include one or more outputdevices 19 to give instructions to the patient and/or medicalprofessional and/or to provide an output configuration for the DBSsystem.

It should be noted that the internal 13 portion is implanted in apatient—with the DBS electrodes 15 in the patient's brain and theneurostimulator being remote from the brain (either external to the bodyor implanted under the patient's skin)—and the external 16 portion isnot implanted in the patient. The external EEG scalp electrodes areillustrated as a plurality of electrodes, but should be understood asincluding any number of electrodes that is limited by the size of thepatient's head and greater than one. Additionally, it should beunderstood that the components of FIG. 1 are not to scale and not shownin their normal positions.

At least one of the components of FIG. 1 (e.g., at least controller 12)can be equipped with a non-transitory memory storing instructions forthe configuration (and in some instances data) and a processor to accessthe non-transitory memory and execute the instructions. Thenon-transitory memory and the processor can be implemented as a singlecircuit, such as an application specific integrated circuit (ASIC), butmay be in any possible implementation of a non-transitory memory and anassociated processor. An input device, such as a mouse or a keyboard,can be a component of controller 12 to allow interaction with thecontroller 12 or any other component the system 10.

The controller 12 can engage in wired and/or wireless communication. Forexample, the controller 12 can communicate with the neurostimulator 14that is implanted internal 13 to the patient's body according to a nearfield wireless communication means (with any necessary additionalcircuitry not illustrated). The external EEG scalp electrodes can beconnected to the controller (through means that may not be illustrated)to engage in wired communication. The controller 12 can be connected tothe task component 18 and/or the output device 19 according to a wiredor wireless connection.

The task component 18 can be one or more instruments configured tomeasure one or more mechanical properties of performing a task that theuser has been instructed to perform. As an example, the task component18 can provide a mechanical or digitized measurement of movement and caninclude a dynameter, digital plate, articulated lever, robotic arm orother mechanical or digitized measurement of movement. This measurementof movement can include, for example, displacement/velocity/accelerationof an extremity or body part, dexterity, strength, resistance (rigidityor spasticity), electromyography, etc. of an extremity or body part.

The system 10 can be used to configure a DBS system to stimulate acerebellar pathway connecting to a brainstem, a diencephalon, or acerebrum of a patient to treat a neurological disorder in the patient.The controller 12 can perform steps related to the configuration,including one or more of: electrical stimulation of any component of aneural pathway associated with the neurological condition, internalrecordings of electrophysiology of sub-cortical areas and/or deep braintissue, external recordings of conduction from the primary motor cortex,secondary motor cortex, primary sensory cortex, and/or secondary sensorycortex, and mechanical measures when performing or attempting to performat least one motor task with a task component. For example, the system10 can be used to execute the process 40 (FIG. 4) described below (orany other process for configuration that uses a different combination ofelectrical stimulation of any component of a neural pathway associatedwith the neurological condition, internal recordings ofelectrophysiology of sub-cortical areas and/or deep brain tissue,external recordings of conduction from the primary motor cortex,secondary motor cortex, primary sensory cortex, and/or secondary sensorycortex, mechanical measures when performing or attempting to perform atleast one motor task, or the like).

As shown in FIG. 2, the controller 12 can have a non-transitory memory22 storing instructions and data and a processor 24. For example, thenon-transitory memory can be a read only memory (ROM), random accessmemory (RAM), magnetic RAM, core memory, magnetic disk storage medium,optical storage medium, flash memory device, and/or other machinereadable mediums (readable by the processor, in other words) for storinginformation, including instructions and/or data. The non-transitorymemory 22 can be associated with a receiver 26. The processor 24 can beassociated with an output 28.

The receiver 26 can receive signals from the internal 13 portion and theexternal 16 portion that include internal data (e.g., electrophysiologydata) and external data (e.g., EEG data). In some instances, thereceiver 26 can also receive data from the task component 18, such asinformation related to one or more mechanical properties of performing atask that the user has been instructed to perform. The processor 24 canuse at least a portion of the data received and provide an output(including a configuration, a task, or the like) to the output 28. Theoutput 28 can provide the output to be output device 19, which canprovide an audio and/or visual output. For example, as shown in FIG. 3,the processor 24 can execute the comparison 30 between one or morefeatures extracted from one or more of the signals (feature extraction32) and one or more templates (biophysical template 34) can be comparedby the comparator 36 and based on the comparison, the parameters of theDBS stimulation can be tuned 38. The tuned parameters can be output bythe output 28.

IV. Methods

Another aspect of the present disclosure can include a method 40 (FIG.4) for configuring a deep brain stimulation (DBS) system to stimulate acerebellar pathway connecting to a brainstem, a diencephalon, or acerebrum of a patient to treat a neurological disorder in the patient.The method 40 can be executed using the system 10 shown in FIG. 1 (withfurther aspects shown in FIGS. 2 and 3).

For purposes of simplicity, the method 40 is shown and described asbeing executed serially; however, it is to be understood and appreciatedthat the present disclosure is not limited by the illustrated order assome steps could occur in different orders and/or concurrently withother steps shown and described herein. Moreover, not all illustratedaspects may be required to implement the method 40, nor is the method 40necessarily limited to the illustrated aspects. Additionally, one ormore of the steps can be stored in a non-transitory memory and accessedand executed by a processor.

As an optional first step (not shown), an initial monopolar review (orelectrical stimulation) can occur to determine any electrode(s) and/orstimulation parameters that cause undesirable side effects. Theseelectrode(s) and/or stimulation patterns can be excluded from thefurther steps of the method 40. The decision to exclude can be specificto the user (e.g., based on symptoms and/or the way the electrodes areimplanted). However, the decision to exclude may be based on (orsupplemented by) data specific to a population that includes at leastone similar patient.

At Step 42, a patient can be instructed to perform one or more motortask. For example, the patient can be instructed to perform the one ormore motor task by a medical professional (e.g., chosen from predefinedmotor tasks based on the medical condition of the patient). As anotherexample, the controller (element 12 of FIG. 1) can determine the one ormotor tasks (based on data input about the patient and/or pastperformance of the patient and/or a population of similar patients) andoutput the instruction related to the one or more motor tasks by audioand/or video (e.g., by output device 19 associated with controller 12).In response, the patient can perform, at least attempt to perform, oreven think about performing the one or more motor task as internal data(e.g., electrophysiology data used in Step 44 and/or external data(e.g., electroencephalography (EEG) data used in Step 46 can be recordedby appropriate electrodes and received (by controller 12). In someinstances, the motor task can be aided by a task component (element 18of FIG. 1) that can also record data related to the motor task.

One or more electrodes are selected to deliver the stimulation by acombination of Step 44 and Step 46. These steps can occur in any order.Additionally, although described as related to the patient performing orattempting to perform the same motor task, it will be understood thatthe Steps can occur with multiple motor tasks, which are either the sameor different. For example, the motor task can include moving an affectedextremity, such as an arm, a hand, a finger, a foot, or a leg. In somepatients, different parts of the same extremity may be affected and/ordifferent extremities may be affected.

At Step 44, internal data (which can be electrophysiology datarecorded/measured by implanted DBS electrodes 15 during the task, e.g.,local field potential (LFP) recordings by implanted DBS electrodesmeasured) can be received/analyzed (by controller 12). The internal datacan reveal which electrode(s) (of the DBS electrodes 15) has a strongestsignal recorded based on the the motor task. The strength of the signalcan be indicated in by a power in a theta, alpha, beta, and/or gammaoscillatory band and/or a power change in an theta, alpha, beta, and/orgamma oscillatory band of each electrophysiology signal (e.g., LFPsignals). The DBS electrodes (DBS electrodes 15) can be implanted in atleast one cerebellar pathway connecting to a brainstem, a diencephalon,or a cerebrum. Based on the electrophysiology data, at least one of theelectrodes can be identified as implanted closest to a neuronalpopulations involved in control of the at least one motor task.

At Step 46, external data (which can be EEG data recorded by at leastone external EEG scalp electrodes—a plurality of external EEG scalpelectrodes are shown as element 17 of FIG. 1) can be received/analyzed(by controller 12). For example, the EEG scalp electrodes (element 17 ofFIG. 1) can be located over the user's primary motor cortex, secondarymotor cortex, primary sensory cortex, and/or secondary sensory cortex.The external data can reveal which electrode provides a change in theexternal data. For example, the change in the EEG data can be a changein event related desynchronization (ERD) and/or event relatedsynchronization (ERS) and/or may be seen in theta, alpha, beta, and/orgramma band activity in the EEG data. Based on the EEG data, at leastone of the electrodes can be identified as causing the change.

The electrode(s) identified as closest to the neuronal populations incontrol of the at least one motor task and the electrode(s) identifiedas causing the change can be compared and the ideal electrode to deliverthe DBS can be chosen. In some instances, the electrode(s) identified asclosest to the neuronal populations in control of the at least motortask can be identified and the electrode(s) identified as causing thechange can be narrowed down to the ideal electrode(s). However, in otherinstances, the electrode(s) identified as closest to the neuronalpopulations in control of the at least motor task and the electrode(s)identified as causing the change can be weighed against one another toselect the ideal electrode(s). It should be noted that the electrode(s)identified as closest to the neuronal populations in control of the atleast motor task and the electrode(s) identified as causing the changemay be compared in different ways to select the electrode(s) to deliverthe DBS stimulation or different data may be used additionally—e.g., insome instances, a change in an instrumentation-based motor behaviorwhile performing the task can be additionally considered in theweighting.

At Step 48, the optimal parameters for the DBS can be determined. Insome instances, the optimal parameters are parameters that provide aresponse indicative of modulation with a lowest magnitude. For example,the optimal parameters comprise an optimal stimulation amplitude, one ormore optimal burst parameters, an optimal stimulation frequency, and anoptimal stimulation pulse width.

The optimal parameters for the DBS and the at least one of the potentialstimulation electrode to deliver the DBS can be output (e.g., by thecontroller 12 to output device 19) for guiding configuration of the DBSsystem for the user. In some instances, these optimal parameters andideal electrodes selected are presented as a check or guide for themedical professional (e.g., the medical professional can try the optimalparameters and ideal settings first). However, in other instances theconfiguration can be done in an automated fashion.

V. Experimental

The following example shows the use of an example of the integratedapproach to configure a deep brain stimulation (DBS) system according tobiomarkers, as described herein.

As new treatments are developed based on deep brain stimulation forneurological disorders like stroke and other non-traditional DBStargets, new challenges arise related to configuring the DBS system inthat the configuration can no longer rely on acute observations toselect ideal electrical stimulation parameters because no acuteimprovements are improved during programming. Instead, biomarkers areneeded that will change acutely in response to different electricalstimulation settings and will predict the long-term outcome adequately.

A first-ever clinical trial of DBS targeting the cerebellar pathwaysconnecting to the cerebral cortex is being conducted with an objectiveof enhancing the outcomes of post stroke rehabilitation and improvingthe patient's quality of life. From this study, data has been collectedthat corroborates the feasibility of this intervention and indicates theidentification of some of such biomarkers to facilitate configuring andprogramming of the DBS system.

As shown in FIG. 5, the approach for configuring the DBS systemincludes: (1) conduct a monopolar review to narrow down possibletherapeutic settings, excluding those that cause acute side effects suchas sensation of pulling, motor changes or any other undesired symptom(step 52—electrode causes side effects? This step is optional.); (2) useinformation gained from electrophysiology (e.g., local field potentials(LFPs)) measured from the DBS electrodes during tasks, such as moving orattempting to move the arm, hand, fingers, foot or leg, which indicateselectrodes that are implanted closest to the neuronal populations mostlyinvolved in motor control and helps select the best electrodes forstimulation out of the multi-electrode leads (step 54—local effects?);(3) test for acute effects of DBS settings on the perilesional cortex orcontralesional cortex using scalp electroencephalography (EEG) measuressuch that DBS settings are selected or refined based on which settingsprovide the most robust changes in event-related desynchronization andevent-related synchronization (ERD and ERS), another indicator of whichelectrodes from the multi-electrode lead are best for stimulation (step56—acute effects?); (4) in some instances, combined with the EEGmeasurements, results of motor behavioral tasks that can indicate themotor performance with greater accuracy and precision than simplenaked-eye observation (e.g., motor speed, grip or extension strength,dexterity, and the like) can be used to further configure the DBS system(optional, may be part of step 56—acute effects?); and (5) stimulationparameters can be optimized (step 58—titrate). The intent is to selectthe lowest amplitude that produces a robust response on the perilesionalcortex, indicative of modulation. Higher amplitudes that produce similarresults are seen as less desirable as they increase the likelihood ofside effects without increments in modulation. The following data isshown related to step (2) (FIGS. 6-8), step (3) (FIG. 9), step (4) (FIG.10), and step (5) (FIG. 11).

Step (2)

FIGS. 6-9 show LFPs recorded from DBS electrodes. This data showsmodulation of LFPs recorded from the cerebellar dentate nucleus duringperformance of a motor task using the effected extremity.

FIG. 6 shows the overall change in alpha and beta band power from LFP(top row), the dynamometer force (middle row), and EMG envelope recordedfrom muscles (bottom row) profile during a motor squeeze task. Thex-axis in all rows is time in seconds for all rows. For the top row, they-axis represents the amount of power present in the LFP signal thatfalls within the traditionally-defined alpha and beta oscillatory bands.

Time 0 is the onset of force production. As depicted, although there wasa modest, initial increase in LFP power during force production, thelargest modulation in LFP was observed during squeeze relaxationstarting at approximately one second after force onset. Note thesignificant change in power in the beta and alpha bands that occur whenthe patient attempts to relax the hand, as shown by the reduction inactivity from the dynamometer and the EMG.

FIGS. 7 and 8 provide an assessment of which specific electrodes arerecording the most significant changes in activity for two differentpatients. This is in addition to the overall changes in alpha and betaband activity shown in FIG. 6. In FIG. 7, the LFP modulation is plottedseparately for each contact pair (there are 8 contacts in the electrodethat was used) when affected (light colored line) and non-affected (darkcolored line) upper extremities performed a motor task. Robustmodulation was seen during tasks with the upper extremity affected bythe stroke in DBS contacts A and B, but not in other contacts,suggesting that A and B are the best contact choices for long-termstimulation. FIG. 8 shows another example of strong activity occurringat the time of movement with upper extremity affected by stroke. Similarto the patient in FIG. 7, for the patient in FIG. 8, the most robustmodulation was seen with contacts A and B.

Step 3

The possible DBS settings identified in Step (2) (and Step (1) if used)can be further tested in Step (3). FIG. 9 shows the acute effects of DBSon scalp EEG metrics. Specifically, task-related changes in the alpha(8-12 Hz) and beta (13-30 Hz) band activity can be recorded using scalpEEG electrodes placed over the contralateral sensorimotor cortex.Typically, task onset is marked by a transient change in power acrossthe alpha/beta bands (event-related desynchronization (ERD)) followed bya rebound change of that power upon task completion (event-relatedsynchronization (ERS)). These two phenomena have been shown to correlatewith motor performance.

Subjects performed motor task with DBS switched OFF and turned ON withone or more of the candidate DBS settings identified. Comparing theERD/ERS magnitude between DBS OFF and ON conditions will provideinformation about the ability of DBS to modulate cortical excitability.FIG. 9 shows Time-Frequency plots derived from time-series recordedusing an EEG electrode over the perilesional cortex. The DBS setting forthe top row is ineffective (e.g., the setting did not modulate ERS overperilesional cortex), while that in the lower row is considered to beeffective (e.g., the setting successfully modulated ERS amplitude in afashion consistent with movement facilitation).

Step 4 (Optional)

In addition to testing acute effects of DBS on EEG based metrics,significant improvements in motor behavior or metrics can beinvestigated. Of note, these are not naked-eye observations as typicalof DBS programming for movement disorders. Rather, they areinstrumentation-based, quantitative, objective metrics of motorfunction.

FIG. 10 shows DBS induced changes in various behavioral metrics. TopRow: shows an exemplar trace from dynamometer during a squeeze task andthe corresponding measures that can be derived. Response time is thetime spanned between GO cue and movement onset. Reach time is the timespanned between onset and target. Relaxation time is the time spannedbetween target and complete session of movement. Relaxation time wasdivided into slow and fast phase based on changes in velocity. Reach andrelaxation rates were computed by normalizing the magnitude of movementby time. The Bottom row shows data from a testing session. The leftpanel shows averaged force data (multiple trials) during DBS OFF and DBSON conditions. The middle panel shows % changes in response times whenDBS was ON compared to DBS OFF. The right panel shows % change inresponse rates when DBS was ON compared to DBS OFF.

Step 5

It is feasible to characterize and quantify the magnitude of the changein cerebral cortical activity evoked by stimulation of the cerebellardentate region as a means of titrating therapeutic charge (pulseamplitude x pulse width) delivery. We have discovered that responses tolow-frequency electrical stimulation of the cerebellar dentate regioncan be time-locked average to yield reproducible spatiotemporal patternof cerebral cortical activity as recorded using surface, or scalp, EEGelectrodes (FIG. 11A). FIG. 11A shows an overview of the recordingset-up, depicting a patient with an existing implanted pulse generatorand DBS lead implant who has been fitted with scalp recordingelectrodes. Stimulus pulses are delivered by the implanted pulsegenerator and detected as electrical artifact in the EEG signal for useas a time-locking signal. In the upper right of FIG. 11A, an examplemapping of responses recorded across multiple EEG electrode sites acrossthe scalp is depicted.

Stimulus pulses may be delivered either by an external pulse generatorin cases where the proximal end of the DBS lead is externalized or usinga previously implanted pulse generator as the source. Analysis of thespatiotemporal distribution of these responses can be used to identifycortical regions that are maximally modulated in response to thestimulus pulse as a function of time post-stimulation (FIG. 11B). Byvarying specific features of stimulation, including pulse amplitude,pulse width, and electrode/contact through which stimulation isdelivered, it is possible to characterize further the degree of corticalmodulation using different quantitative metrics (e.g., RMS power,peak-to-peak amplitude, peak latency). In FIG. 11B, the upper drawingrepresents a butterfly plot, which overlays the averagedelectroencephalographic response recorded from multiple sites across thescalp to a single set of DBS parameters. The stimulus pulse (denoted bythe star) evokes a complex, multi-phase response that lasts for morethan 100 ms post-stimulation (settings: 2.0 mA delivered at90-microsecond pulse width). Current source density maps (bottom)highlight potential regions of interest for further characterizingchanges in the evoked response as a function of pulse amplitude/widthand further highlight the possibility of using the DBS evoked potentialresponse to visualize how changes in DBS parameters steer the modulationof activity across different cortical regions.

FIG. 11C demonstrates how the overall size of the evoked responsechanges as a function of pulse amplitude for a single recording site(EEG site FC2) when the pulse width is maintained at 90 microseconds andthe same electrode/contact is used so that electrode/contact and pulsewidth are consistent in this figure. In FIG. 11C, the averaged evokedresponse recorded from the FC2 recording site is plotted (amplitude (μV)v. time (ms)) for multiple conditions of pulse amplitude ranging from1.0 mA to 9.0 mA. The response at 2.0 mA and 6.0 mA is highlighted forillustration purposes and the peaks used to calculate peak-to-peakamplitude changes as a function of changes in pulse amplitude arehighlighted (N1: 1^(st) negative peak; P1: 1^(st) positive peak; N2:2^(nd) negative peak).

Notably, for a given pulse width, the relationship between the responseamplitude and pulse amplitude is non-linear and typically marked by aninitial steep phase where the magnitude of the evoked response increasesrapidly per unit increase in pulse amplitude, followed by a phase wherethe growth in magnitude is reduced per unit of amplitude increase (FIG.11D). In practice, such a response may be used to identify, at apatient-specific level, the pulse parameters that maximize the inducedcortical modulation without saturating the system. Data for making thisdetermination may be derived from a single channel or a combination ofdata from multiple recording electrodes. In addition to optimizing thedegree of neuromodulation the system would also improve therapeuticefficiency by minimizing the risk of waste charge delivery (e.g.,additional charge that does substantially amplify the corticalresponse). In FIG. 11D, the peak-to-peak amplitude of the majorcomponents of the evoked response plotted as a function of cerebellarstimulus pulse amplitude for P1 minus N1 (left) and N2 minus P1 (right).It is noteworthy that both metrics suggest the onset of a plateau in themodulatory effects of DBS at pulse amplitudes above 4.0 mA, which may beuseful in identifying the optimal, therapeutic stimulus amplitude.

From the above description, those skilled in the art will perceiveimprovements, changes and modifications. Such improvements, changes andmodifications are within the skill of one in the art and are intended tobe covered by the appended claims.

The following is claimed:
 1. A method for configuring a deep brainstimulation (DBS) system for a patient, the method comprising:instructing the patient to perform or attempt to perform at least onemotor task; in response to the patient performing or attempting toperform the at least one motor task, receiving, by a system comprising aprocessor, electrophysiology data from a plurality of DBS electrodesimplanted in at least one cerebellar pathway connecting to a brainstem,a diencephalon, or a cerebrum of the patient; based on theelectrophysiology data, identifying, by the system, at least one of theplurality of electrodes implanted closest to a neuronal populationsinvolved in control of the at least one motor task as potentialstimulation electrodes; in response to the patient performing orattempting to perform the at least one motor task, receiving, by thesystem, electroencephalogram (EEG) data corresponding to at least onescalp EEG from a plurality of scalp electrodes; based on the EEG and/orDBS electrode data, selecting, by the system, at least one of thepotential stimulation electrodes to deliver the DBS based on which ofthe potential stimulation electrodes provides a change in the EEG dataand/or DBS electrode data; and determining, by the system, optimalparameters for the DBS by the at least one of the potential stimulationelectrodes, wherein the optimal parameters for the DBS and the at leastone of the potential stimulation electrode to deliver the DBS are outputfor guiding configuration of the DBS system for the patient.
 2. Themethod of claim 1, further comprising configuring the DBS system, by thesystem, so that the at least one of the potential stimulation electrodesdelivers the DBS at the optimal parameters.
 3. The method of claim 1,wherein the at least one motor task comprises moving an arm, a hand, afinger, a foot, or a leg.
 4. The method of claim 1, wherein theelectrophysiology data comprises one or more local field potentials(LFPs) measured by the plurality of DBS electrodes during the at leastone motor task.
 5. The method of claim 4, wherein the electrophysiologydata comprises a power in a theta, alpha, beta, and/or gamma oscillatoryband of each LFP signal and/or a power change in an theta, alpha, beta,and/or gamma oscillatory band of each LFP signal.
 6. The method of claim1, wherein the EEG electrodes are located over the patient's primarymotor cortex, secondary motor cortex, primary sensory cortex, and/orsecondary sensory cortex.
 7. The method of claim 1, wherein the changein the EEG data is a change in event related desynchronization (ERD)and/or event related synchronization (ERS).
 8. The method of claim 7,wherein the change in the EEG is seen in theta, alpha, beta, and/orgramma band activity in the EEG data.
 9. The method of claim 1, whereinthe selecting at least one of the potential stimulation electrodes todeliver the DBS is further based on a change in an instrumentation-basedmotor behavior.
 10. The method of claim 1, wherein the optimalparameters are parameters that provide a response indicative ofmodulation with a lowest magnitude of stimulation.
 11. The method ofclaim 1, wherein the optimal parameters comprise at least one of anoptimal stimulation amplitude, one or more optimal pulse or burstparameters, an optimal stimulation frequency, and an optimal stimulationpulse width.
 12. The method of claim 1, before the instructing,excluding at least a portion of the plurality of DBS electrodes and/orstimulation parameters known to cause undesired side effects.
 13. Themethod of claim 12, wherein the excluding is based on an initialmonopolar review specific to the patient.
 14. The method of claim 12,wherein the excluding is based on data specific to a populationcomprising at least one similar patient.
 15. A system that configures adeep brain stimulation (DBS) system for a patient, the systemcomprising: a memory storing instructions; a processor to access thememory and execute the instructions to: in response to the patientperforming or attempting to perform the at least one motor task, receiveelectrophysiology data from a plurality of DBS electrodes implanted inat least one cerebellar pathway connecting to a brainstem, adiencephalon, or a cerebrum of the patient and electroencephalogram(EEG) data corresponding to at least one scalp EEG from a plurality ofscalp electrodes; based on the electrophysiology data, identify at leastone of the plurality of electrodes implanted closest to a neuronalpopulations involved in control of the at least one motor task aspotential stimulation electrodes; based on the EEG data, select at leastone of the potential stimulation electrodes to deliver the DBS based onwhich of the potential stimulation electrodes provides a change in theEEG data and/or DBS electrode data; and determining optimal parametersfor the DBS by the at least one of the potential stimulation electrodes,wherein the optimal parameters for the DBS and the at least one of thepotential stimulation electrode to deliver the DBS are output forguiding configuration of the DBS system for the patient.
 16. The systemof claim 15, wherein the processor further executes the instructions toconfigure the DBS system so that the at least one of the potentialstimulation electrodes delivers the DBS at the optimal parameters. 17.The system of claim 15, wherein the electrophysiology data comprises oneor more local field potentials (LFPs) measured by the plurality of DBSelectrodes during the at least one motor task.
 18. The system of claim15, further comprising the EEG electrodes, and a task componentconfigured to assist the patient in performing or attempting to performthe at least one motor task.
 19. The system of claim 15, wherein theoptimal parameters are parameters that provide a response indicative ofmodulation with a lowest magnitude of stimulation.
 20. The system ofclaim 15, wherein the processor further executes the instructions toexclude at least a portion of the plurality of DBS electrodes and/orstimulation parameters that cause undesired side effects based on aninput received from a medical professional, an instrument monitoringbehavior of the patient, or the patient.